Radioactive therapeutic device with fixation

ABSTRACT

Devices and techniques for permanent application of radioactive sources in the field of brachytherapy are described. In an embodiment, an implantable device for radiation therapy of pathological tissues directed toward the administration of radiation to tissue adjacent a cavity wall or surgical excision. The device may include an insertable member, such as a substantially cylindrical member, having at least two ends, a central section positioned between the ends, and a fixation element to retain the implantable device implanted in tissue at a desired position. The device may further include a radioactive source at least partially positioned within the insertable member and that is disposed to deliver radiation to a desired area.

RELATED APPLICATIONS

This application claims priority to U.S. Provisional App. No.61/837,409, filed on Jun. 20, 2013, entitled “Radioactive TherapeuticDevice with Fixation,” which is incorporated herein by reference.

TECHNICAL FIELD

This application relates to the field of brachytherapy, particularly thefield of radiation treatment of cancerous tissue that would occur in thebody by placing radioactive sources in or near the cancerous tissue.

BACKGROUND OF THE INVENTION

Ionizing radiation is employed in the management of a wide variety ofmalignant tumors, providing a mechanism whereby the malignancy can bedestroyed while the normal tissues are preserved. With preservation ofnormal tissues, normal function and normal appearance may also bepreserved. Hence, ionizing radiation forms part of the treatment forover half of all patients with cancer. The overall effectiveness ofradiation therapy, however, depends upon the balance between effectivetumor control and morbidity due to the treatment. It is understood thatthe differential effects of ionizing radiation on tumors and normaltissues gives rise to a favorable therapeutic ratio for most patients.However, radiation can have destructive immediate and delayed effects onnormal tissues. Techniques employed for radiation therapy significantlyaffect the incidence and severity of these destructive effects.

Various techniques have been developed to treat tumors in the body. Ingeneral, the use of radiation to reduce or eliminate malignancy has beenknown for many years. One of the major issues in all of the techniquesis the prevention of damage to healthy tissue. Because all types ofionizing radiation affect tissues by means of the same basic physicalmechanisms, differences in spatial or temporal distributions areresponsible for different effects observed. The method for deliveringradiation thus becomes highly significant.

The type of radiation treatment of malignant tumors most often performedinvolves directing a beam of radiation from a point external to thepatient's body onto the area of the body in which the tumor is located,for the purpose of shrinking and ultimately destroying the tumor. Thistechnique is known as “teletherapy” or external beam radiation therapy.Such treatment exposes normal healthy tissue to a high dose of radiationin the beam and consequently subjects the normal tissue to potentialinjury. Conventional external beam radiation treatments rely on multiplefractions of dose in order to ensure that the highest fractions of tumorcells are exposed at the most sensitive parts of the cell life cycle.

In contrast to external beam radiation therapy, brachytherapy is amethod of radiation treatment of cancerous tissue in which theradioactive source is placed in or near the cancerous tissue. Because ofthe proximity of the radioactive source to the target tumor or canceroustissue, brachytherapy treatment permits administration of a higherradiation dose to the tumor with better sparing of surrounding normalhealthy tissues.

Because a delivered dose from a radioactive source decreasesproportionately to the square of the distance from that source,brachytherapy permits the delivery of very high radiation doses to thoseareas of a tumor in close proximity to the source, with relative sparingof more distant tissues. With careful placement, so that the radioactivesource is in proximity to the tumor or target tissue and distant fromnormal tissue, effective therapy against the tumor may be combined withminimal collateral damage to normal tissues.

Brachytherapy came into use as a treatment tool for cancer soon afterthe discovery of radium by Marie Curie in 1898. Goldberg and London usedit for the treatment of facial basal cell carcinomas in 1903 withsurface applicators. Brachytherapy can be applied to cancer either bypermanent implantation or by temporary application of removable sources.Permanent implantation results in the radioactive source, or sources,being left in the body in perpetuity, delivering their radiation doseuntil the radioactive material in the source has completely decayedaway.

A variety of radionuclides and methods for permanent or temporaryimplantation have been developed. For example, a variety ofradioisotopes, including 125Iodine, 103Palladium, 198Gold 131Cesium,137Cesium, 60Cobalt, 169Ytterbium and 192Iridium, have been used in thetreatment of cancers involving such tissues as the breast, the prostate,the brain, lung, the head and neck, the female reproductive tract, themusculoskeletal system and related soft tissues, and the eye. Examplesof radioactive sealed sources employed in brachytherapy and intended forpermanent implantation are discussed in B. H. Heintz et al., “Comparisonof I-125 sources used for permanent interstitial implants,” MedicalPhysics, Vol. 28, No. 4, April 2001, pp. 671-682, the contents of whichare hereby incorporated by reference.

Certain devices known in the prior art are intended for insertion ofbrachytherapy sources directly into the tissues without employing aneedle or other similar delivery device. An example of such a device maybe found in the disclosure of U.S. Pat. No. 4,815,449 to Horowitz, whichis incorporated herein by reference. This patent provides, in certainembodiments, an implant of sufficient rigidity to be driven into a tumorwithout deflection, so that the implant may be used independently of apositioning or delivery device.

Alternatively, brachytherapy sources may be positioned in the tissues tobe treated by insertion through a delivery device, for instance, aneedle. This technique is common, for example, in the treatment ofprostate cancer. Using a delivery device may allow precise positioningof sources in areas requiring treatment. Brachytherapy sources fromvarious manufacturers may be made to the same set of specifications sothat they are compatible with those delivery systems in common use. Inthose delivery systems, the sources may be preloaded into needles orother delivery devices. The position of a plurality of sources withinthe delivery device may be maintained by placing loose spacers betweenthe sources to establish and maintain a desired positioning. Once thesources are positioned in the delivery device, insertion into thetissues takes place. To insert the sources, the needle containing themmust first be inserted to a preselected depth into the appropriatepositioned in the patient's tissues.

An injection mechanism such as a mandrel may then be inserted into theneedle with its distal end in contact with the linear array of sources.The needle, thereafter, may be withdrawn over the mandrel, leaving thesources and loose spacers resident in the preselected tissue area. Oncepositioned within the tissues using this method, the sources and loosespacers are free to move from their original position, as there are noconstraints on the position or orientation of the sources other than thefriction of the tissue itself in contact with the surfaces of thesources. Such movement can lead to the undesirable consequence that dosedistribution within the tissue may be changed, for instance, movement ofthe sources after deployment can change the area being irradiated, andcan change the dose being delivered both to the preselected tumorregions and to the surrounding normal tissues.

Numerous approaches to solve this problem have been developed. In orderto maintain the radioactive sources and spacers in their appropriaterelative positions, devices have been designed to join these sources andspacers together. Examples of such devices are described in U.S. Pat.No. 6,709,381 to Munro, U.S. Pat. No. 6,820,318 to Terwilliger et al.and U.S. Pat. No. 6,010,446 to Grimm, which are all incorporated hereinby reference. These devices preserve the relative linear positioning ofthe multiple sources, but provide only limited resistance tolongitudinal movement.

A number of approaches have been utilized to prevent furtherdisplacement of the sources. Examples include U.S. Pat. No. 8,114,007 toLamoureux et al. and U.S. Pat. No. 8,366,598 to Lamoureux et al., whichare incorporated herein by reference, which describe a source or sourcesmolded within a polymeric material to encapsulate the radioactivesources and includes a plurality of protrusions on the outer surface ofthe encapsulating polymeric material to resist migration and rotation.

Another example is U.S. Pat. No. 4,936,823 to Colvin et al., which isincorporated herein by reference, which describes resilient arms whichcan be manipulated to anchor a body containing a radioactive sourcewithin a body canal. Further, U.S. Pat. No. 6,264,599 to Slater et al.,which is incorporated herein by reference, describes a method similar toColvin '823 except that Slater '599 provides for automaticallypositively engaging the resilient arms into the tissue.

All of these methods require substantial tissue surrounding the sourcesto prevent lateral movement and to provide resistance to the deploymentof the resilient arms or the protrusions of the polymeric extrusions.Although these methods are, in many cases, sufficient when placing thebrachytherapy source into massive tumor or tumor tissue itselfsurrounded by healthy tissue, there exist cases where treatment isdesired after surgical removal/resection of the tumor.

Gross surgical removal of tumor tissue can leave behind traces of tumor,precancerous, or other diseased tissue which can foster recurrence ormetastasis of the tumor. Accordingly, the site of removal of a tumor isoften treated postoperatively in an attempt to destroy any such diseasedtissue left behind by the surgery. Conventional techniques for treatingthe site of surgical removal of a tumor include post-operativeadministration of radiation, chemotherapy, and/or heat.

Although external beam therapy and short-range therapy are two commonlypracticed techniques for administration of post-operative radiation,external beam is less desirable. In external beam therapy, also known asteletherapy, an external radiation beam is directed at the treatmentsite. In teletherapy, the radiation beam must be carefully positionedwith respect to the treatment site to minimize the radiation exposure ofthe surrounding healthy tissue. Even with a high degree of precision,however, healthy tissue in the vicinity of the treatment site mayreceive significant doses of radiation. This side effect can becompounded when treatment requires repeated administrations, eachrequiring careful positioning of the radiation beam.

In short-range brachytherapy, radioactive sources are placed at or nearthe treatment site, i.e. the region adjacent to the surgical resection,to provide site-specific delivery of radiation therapy, potentiallyreducing undesirable side effects associated with teletherapy, such asirradiation of healthy tissue. One common brachytherapy technique usescatheters to deliver temporary radiation to the treatment site. In thistechnique, numerous catheters may be simultaneously inserted into oraround the treatment site, sewn into place, loaded with solid isotopicpellets for a prescribed time, and then removed. The process of placinga number of catheters simultaneously within the appropriate region iscumbersome and time-intensive. Additionally, invasive insertion andexternal exposure of the catheters presents an increased risk ofinfection to the patient, and can result in significant discomfort forthe patient during treatment. Finally, any subsequent treatment, forexample, treatment following tumor recurrence, requires that the entireprocess be repeated from the beginning. For these reasons, temporarybrachytherapy is not a desirable treatment method.

A common brachytherapy technique employs radioactive implants to deliverpermanent radiation therapy. In this technique, numerous radioactivesources are implanted directly into or around the treatment site.However, as the tumor, in these cases, has already been surgicallyremoved and the desired treatment is to the limited amount of tissueadjacent to the surgical resection, there is insufficient tissue in theregion of the target to employ the methods described above, namelyrelying on the pressure of the surrounding tissue to render theirregular surface to be immobile, as described by Munro '381,Terwilliger '318, Grimm '446, Lamoureux '007, or Lamoureux '598, or toprovide tissue around the source in all directions to provide means forresilient arms to engage, as described by Colvin '823 or Slater '599.

In limited cases, a device for providing radiation treatment to atreatment site that can be implanted at the time of tumor removal andwhich delivers a relatively uniform dose of radiation throughout thesurrounding tissue as described by U.S. Pat. No. 6,527,693 to Munro etal., which is incorporated herein by reference. However, in many cases,such as the lung, the residual tissue remaining after resection andrequiring treatment is irregularly shaped and cannot be treated usingthe method described by Munro '693.

Methods to affect this type of treatment have been described. Referenceis made to W. Lee et al., “Limited resection for non-small cell lungcancer: observed local control with implantation of 125I brachytherapyseeds,” Annals of Thoracic Surgery 75(1), January 2003, pp. 237-242,which is incorporated herein by reference, in which is described abrachytherapy technique that uses strands of ten 125Iodine seeds,embedded in polyglactin 910 suture with 1 cm spacing which were affixedby suture along the resection margin or 0.5 cm on either side of themargin. Reference is also made to A. Chen et al., “Intraoperative 125Ibrachytherapy for high-risk stage I non-small cell lung carcinoma,” Int.J. Radiation Oncology Biol. Phys., Vol. 44, No. 5, 1999, pp. 1057-1063,which is incorporated herein by reference, in which is described analternative method utilizing vicryl surgical mesh imbedded with stranded125Iodine radioactive seeds placed over the tumor bed and surgicalresection line and sutured in place. Both of these methods requiremanual suturing of the strands or mesh in place. The difficulty ofprecisely delivering the brachytherapy sources intraoperatively toachieve the proper dose distribution and minimizing the radiation doseto the clinicians performing the procedure make these techniques lessdesirable.

An improved method for delivering a brachytherapy source has beendescribed in U.S. Pat. Nos. 7,604,586, 7,972,260, and 8,267,849, all toWazer et al., which are incorporated herein by reference, in which theradioactive sources are incorporated directly into a subset of thesurgical staples used in the procedure. In this way, the sources aresecured in position directly adjacent to the surgical resection and areimmobile. This method facilitates the precise placement of brachytherapysources relative to the surgical margin, assures the seeds remain fixedin their precise position for the duration of the treatment, overcomesthe technical difficulties of manipulating the seeds through the narrowsurgical incision, and reduces the radiation dose to the clinicians.However, this method also has a number of drawbacks.

In particular, the concept of delivering the radioactive sourcestemporally and spatially adjacent to the surgical resection is oflimited value. In practice, most procedures remove the suspected tumortissue (and therefore remove the surgical stapling/resection device) andawait pathological analysis before deciding to perform brachytherapy.Physicians do not want to introduce brachytherapy sources into thepatient until it has been determined that the tissue is malignant.Therefore, the advantage of having the brachytherapy source deliverydevice physically aligned with the surgical stapling/resection device islost.

The attachment of a brachytherapy source delivery device to the surgicalresection device/stapler also has several other disadvantages. Itprovides a more cumbersome device for the surgeon to manipulate, and mayintroduce difficulties introducing the assembly through standardthoroscopic ports. It can also interfere with surrounding tissue,leaving less margin around the suspect tumor from which to excise. Thereis also risk that the brachytherapy source delivery device coulddislodge from the surgical resection device/stapler, therebycomplicating the procedure.

By design, “staple-like” brachytherapy sources are delivered on theactive-lung side of the surgical staple line (as the surgical resectionis immediately adjacent to the surgical staples on the other side). Thisrequires the staple-like brachytherapy sources to pierce the lung,introducing the potential for air leakage. Furthermore, the strength ofthe closure of the staple-like brachytherapy sources is critical. As thelung cyclically inflates, it cyclically applies force to the sourceclosure. If the closure is insufficient, the staples can becomeunattached and “free-floating.” Furthermore, this force on the stapleclosure can cause damage to adjacent lung tissue, such as by tearing.This is particularly critical as the tissue is often diseased orpathologic.

The use of staple-like brachytherapy sources requires access to bothsides of the tissue through which the source will be deployed. Thestaple-like brachytherapy sources are pushed through the tissue from oneside and an anvil-like element is positioned on the opposite side toaffect the bending and securing of the source. The amount of tissuebetween the two elements must be within a very narrow limited range inorder for the staple-like brachytherapy sources to be properly bent andsecured. If the tissue is too thick, or the anvil-like element does notassume the proper spacing, the staple-like brachytherapy sources can beincorrectly deformed and not secured, leaving them loose to move aboutthe patient. This can also be a concern if there are areas where notissue exists between the two elements of the brachytherapy deliverydevice. This will leave sources free-floating within the patient.

Accordingly, there remains a need for a system which can easily deployand retain the brachytherapy sources in the desired treatment positionadjacent to a surgical resection which alleviates the problemsassociated with the above-delineated systems.

SUMMARY OF THE INVENTION

According to the system described herein, an implantable device forbrachytherapy includes an insertable member having at least two ends, acentral section positioned between the ends, and a fixation element thatretains the implantable device in an inserted position within tissue. Aradioactive source is disposed within the insertable member. Thefixation element may include a helical coil configuration of theinsertable member, in which the helical coil configuration enablestwisting of the insertable member for insertion of the implantabledevice in the tissue and to provide a desired positioning of theradioactive source. The insertable member may be made of a memory alloy,and the fixation element may include a first shape of the insertionmember for insertion into the position within the tissue and a secondshape into which the insertable member forms after insertion into theposition. The memory alloy may include Nickel Titanium or nitinol.Alternatively and/or additionally, the fixation element may include atleast one barbed protrusion, and/or a plurality of barbed protrusions,on at least one of the at least two ends of the insertable member. Thefixation element may include a helical coil configuration of theinsertable member, wherein the helical coil configuration enablestwisting of the insertable member for insertion of the implantabledevice in the tissue and to provide a desired positioning of theradioactive source, and the insertable member may further include atleast one barbed protrusion on at least one of the at least two ends ofthe insertable member. The radioactive source may be completely orpartially encapsulated within the insertable member. The insertablemember may include a chamber with at least one cut-out for externalaccessibility, and in which the radioactive source is partiallyencapsulated within the insertable by being disposed within the chamberwith the at least one cut-out. The radioactive source may beencapsulated within the fixation element. The fixation element mayinclude at least one barbed protrusion, and the radioactive element maybe encapsulated within at least a portion of the barbed protrusion. Theradioactive source may include a radioactive nuclide selected from atleast one of: palladium-103, iodine-125, gadolinium-153, samarium-145,cesium-131 or ytterbium-169.

According further to the system described herein, a method ofmanufacturing an implantable device for brachytherapy includes formingan insertable member of the implantable device for insertion into anarea of tissue. A radioactive source is encapsulated in the implantabledevice. A fixation element is incorporated into the insertable memberfor fixing the radioactive source at a desired location in the area ofthe tissue. The insertable member may be made of a memory alloy. Thefixation element may be a helical coil configuration of the insertablemember, and in which the helical coil configuration enables twisting ofthe insertable member for insertion of the implantable device into thearea of tissue and to provide a positioning of the radioactive source atthe desired location. The fixation element may include at least onebarbed protrusion on the insertable member. The radioactive source maybe completely encapsulated in the insertable member or the fixationelement.

According further to the system described herein, a method forperforming brachytherapy includes identifying an area of tissue forbrachytherapy. An implantable device is inserted into the area of thetissue, in which the implantable device includes a fixation element anda radioactive source encapsulated within the implantable device. Theimplantable device is fixedly disposed using the at least one fixationelement such that the radioactive source is fixed in a position fordelivering radiation therapy to the desired tissue. The implantabledevice may be made of a memory alloy, and in which the implantabledevice is fixedly disposed by thermal processing after inserting theimplantable device into the area of the tissue. The implantable devicemay have a helical coil shape that enables twisting of the insertablemember for insertion of the implantable device in the tissue and toprovide a desired positioning of the radioactive source. The insertablemember may further includes at least one barbed protrusion on at leastone end of the insertable member.

BRIEF DESCRIPTION OF THE DRAWINGS

Embodiments of the system described herein will now be explained in moredetail in accordance with the figures of the drawings, which are brieflyexplained as follows.

FIGS. 1A and 1B are schematic illustrations of an implantable device inthe form of a helical coil which contains an encapsulated radioactivesource according to an embodiment of the system described herein.

FIGS. 2A and 2B are schematic illustrations showing another embodimentof the system described herein for an implantable device in which asingle wire is made from implantable memory alloy.

FIGS. 3A and 3B are schematic illustrations showing another embodimentof the system described herein as a barbed holder that may have anencapsulated radioactive source.

FIGS. 4A and 4B are schematic illustrations showing a barbed holder withcut-outs or windows which contain an encapsulated radioactive sourceaccording to another embodiment of the system described herein.

FIGS. 5A and 5B are schematic illustrations showing a barbed holder inwhich is incorporated a radioactive element such that the barbed holderitself becomes an encapsulated radioactive source according to anembodiment of the system described herein.

FIG. 6 is a schematic illustration showing shows multiple barbs of abarbed holder protruding in multiple directions according to anembodiment of the system described herein.

FIG. 7 is a schematic illustration of a barbed holder having multiplebarbs in an array on one side of the barbed holder according to anotherembodiment of the system described herein.

FIG. 8 is a schematic illustration of a barbed holder having multiplebarbs protruding in multiple directions from the barbed holder accordingto an embodiment of the system described herein.

FIG. 9 is a schematic illustration of a barbed holder comprised ofmultiple barbs disposed on a helical coil like that described elsewhereherein to prevent the coil, with encapsulated radioactive source, fromunscrewing and/or otherwise dislodging from the tissue according to anembodiment of the system described herein.

FIGS. 10A-10C shows formation of a barbed protrusion on a barbed holderaccording to an embodiment of the system described herein.

FIG. 11 is a schematic illustration showing that a barbed protrusion maybe formed on one end of a barbed holder and the other end of the holder,with a radioactive source therebetween, being simply plugged accordingto an embodiment of the system described herein.

FIG. 12 is a schematic illustration showing a barbed holder withmultiple end protrusions according to an embodiment of the systemdescribed herein.

FIG. 13 is a schematic illustration showing a barbed holder showingmultiple protrusions in which both of the protrusions are formed to bepointed, which would permit the holder and radioactive source to beinserted in either direction according to an embodiment of the systemdescribed herein.

FIGS. 14A-14C are schematic illustrations showing embodiments forfabrication of a barb for a barbed holder according to the systemdescribed herein.

FIGS. 15A and 15B shows a barbed holder in which a barb is attached tothe holder by welding to a protrusion from the body of the sourceencapsulation according to an embodiment of the system described herein.

FIG. 16 is a flow diagram for a method for producing an implantabledevice for brachytherapy according to one or more embodiments of thesystem described herein.

FIG. 17 is a flow diagram for a method for brachytherapy according to anembodiment of the system described herein.

DETAILED DESCRIPTION OF VARIOUS EMBODIMENTS

The system described herein provides for devices and techniques forpermanent application of radioactive sources in the field ofbrachytherapy. In an embodiment, an implantable device for radiationtherapy of pathological tissues directed toward the administration ofradiation to tissue adjacent a cavity wall or surgical excision. Thedevice may include an insertable member, such as a substantiallycylindrical member, having at least two ends, such as opposing ends, acentral section positioned between the ends, and a fixation element toretain the implantable device implanted in tissue at a desired position.The device may further include a radioactive source at least partiallypositioned within the insertable member and that is disposed to deliverradiation to a desired area.

The radioactive source may be encapsulated by an outer portion of theinsertable member, e.g., positioned in a chamber spatially located froma periphery of the outer portion. A radioactive source may be aradioactive nuclide that decays by electron capture without the emissionof beta particles or may be a radioactive nuclide that decays with theemission of beta particles. Such a radioactive nuclide may decay withthe emission of gamma rays and/or X-rays, for example, having a weightedaverage energy from about 20 keV to about 100 keV. The radioactivenuclide may be selected from palladium-103, iodine-125, gadolinium-153,samarium-145, cesium-131 and ytterbium-169.

In accordance with another embodiment, the system described hereinprovides a method for the treatment of tissue adjacent a cavity wall.Such a method may include identifying a cavity within a body of tissue,e.g., by removing a portion of tumorous tissue within a body of tissueso as to generate a cavity. The method may also include placing withinthe remaining adjacent tissue an implantable device, such as describedelsewhere herein, having a fixation and at least one radioactive source,e.g., in which the outer portion has a fixation sufficient forimplantation adjacent to or into the cavity wall, and the radioactivesource is positioned within an area spatially located from a peripheryof the outer portion for delivering radiation therapy to the tissueadjacent the cavity wall.

FIGS. 1A and 1B are schematic illustrations of an implantable device inthe form of a helical coil 100 (e.g., a helical clip or tack) whichcontains an encapsulated radioactive source 110 according to anembodiment of the system described herein. FIG. 1B is a section view ofthe helical coil 100 shown in FIG. 1A. In the illustrated embodiment,the helical coil 100 is substantially cylindrical member having at leasttwo ends, a central section positioned between the ends, and a fixationelement in the form of the helical coiled configuration of the coil 100.The radioactive source 110 may be incorporated into and/or onto thehelical coil 100 such that it may be rotated into and through a thinsegment of tissue. In various embodiments, the source 110 may be locatedat the end of the helical coil 110 and/or located between the ends ofthe coil 100. The coil 100 may be affixed to tissue by engaging theleading end of the coil 100, that may be sharpened or pointed, through asegment of tissue and then rotating the coil 100 to cause additionalmaterial to pass through the tissue.

In an embodiment, the coil 100 may be made from any implantable materialincluding “memory” alloys such as a Nickel Titanium or nitinol. The coilmade from memory metal may be made to tighten its hold on tissue afterimplantation due to thermal transition. The transition may also enablehiding the pointed end of the coil 100 to keep it from piercingunintended targets. The coil 100 may even be implanted while at atemperature below ambient room, and well below body temperature, tomaximize the thermal-mechanical transition. This would be beneficial forvery thin tissues and also for locations that are prone to cyclic motiondue to normal body functions such as general mobility & bodily functionslike swallowing, pumping blood, and digesting.

In various embodiments, the nitinol may be used in contact with the bodytissue, or it may be coated, clad or otherwise covered to provide formore lubricious (slippery) coating for ease of application, or a moreresistive coating to resist migration. Further, the nitinol may serve asthe primary encapsulation of the radioactivity, or it may serve as anouter carrier for a previously encapsulated radioactive source.

FIGS. 2A and 2B are schematic illustrations showing another embodimentof the system described herein for an implantable device in which asingle wire 200 is made from implantable memory alloy such as a NickelTitanium or nitinol. FIG. 2B is a view of the single wire shown in FIG.2A after the memory alloy has been bent into a non-straightconfiguration according to shape-memory of the alloy. The single wiremay be inserted into tissue in the straight configuration at roomtemperature and bend into the non-straight configuration when reachingnormal body temperature, thereby establishing its hold on tissue afterinsertion due to thermal transition. In the illustrated embodiment, anencapsulated radioactive source 210 may be incorporated into and/or ontothe single wire 200. In various embodiments, the nitinol may serve asthe primary encapsulation of the radioactivity, or it may serve as anouter carrier for a previously encapsulated radioactive source. Asdiscussed elsewhere herein, the nitinol may be used in contact with thebody tissue, or it may be coated, clad or otherwise covered to providefor more lubricious (slippery) coating for ease of application, or amore resistive coating to resist migration. In addition to the use ofnitinol for shape-memory configuration of the device, this thermaltransition fixation may be achieved using a more traditional bi-metallicjunction such as is employed in a typical thermostat or thermal switch.

FIGS. 3A and 3B are schematic illustrations showing another embodimentof the system described herein as a barbed holder (and/or harpoon) 300that may have an encapsulated radioactive source 310, for example,incorporated as a capsule appended thereto, and/or otherwise attached tothe barbed holder 300, such that the barbed holder 300, with appendedradioactive source 310, may pushed into and through a thin segment oftissue. FIG. 3B is a section view of the barbed holder 300 shown in FIG.3A. The barbed holder 300 may be affixed to tissue by pushing theleading (pointed) end of the barbed holder 300 through a segment oftissue and one or more barbs 301 would cause resistance to removalthrough the aperture created by the deployment. In the illustratedembodiment, the encapsulated radioactive source 310 is shown completelyencapsulated within the barbed holder 300. Although the figure shows theencapsulated radioactive source 310 attached to one end of the barbedholder 300, it is noted that the encapsulated radioactive source may beattached to a side of the barbed holder 300, and that the barbed holder300 may be aligned parallel to the axis of the encapsulation, alignedperpendicular to the axis of the encapsulation and/or aligned at anyangle between parallel and perpendicular.

FIGS. 4A and 4B are schematic illustrations showing a barbed holder 400with cut-outs or windows 402 which contain an encapsulated radioactivesource 410 according to another embodiment of the system describedherein. FIG. 4B shows a section view of the barbed holder 400 of FIG.4A. The holder 400 may include one or more barbs 401, like thatdiscussed in connection with the holder 300, but, rather than requiringcomplete encapsulation of the radioactive source 410, it is possible forthe holder 400 to engage only one end of the radioactive source 410, orengage both ends, with cut-outs or windows 402 a, 402 b in the sides ofthe holder 400.

FIGS. 5A and 5B are schematic illustrations showing a barbed holder 500in which is incorporated a radioactive source element 510 such that thebarbed holder itself becomes an encapsulated radioactive sourceaccording to an embodiment of the system described herein. FIG. 5B showsa section view of the barbed holder 500 shown in FIG. 5A. In theillustrated embodiment, by incorporating radioactivity into the barbedholder 500, such that the radioactive element 510 is inside the body ofthe holder 500, the barbed holder 500 as encapsulated source may bepushed into and through a thin segment of tissue. The holder 500 wouldbe affixed to tissue by pushing the leading (pointed) end of the holderthrough a segment of tissue and the barb would cause resistance toremoval through the aperture created by the deployment. In thisembodiment, the barbed holder 500 itself, and/or at least a portion ofthe barbed protrusion of the barbed holder 500 in which the radioactivesource is encapsulated, thereby becomes the brachytherapy source.

FIG. 6 is a schematic illustration showing shows multiple barbs of abarbed holder 600 protruding in multiple directions according to anembodiment of the system described herein. For example, the barbedholder 600 may have two barbs 601, 602 positioned on either side of anencapsulated radioactive source 610. In an embodiment, as illustrated,the barbed holder 600 may be bent along its length (staple-like) topermit both barbs 601, 602 to be simultaneously engaged. In otherembodiments, the barbed holder 600 may not be bent and/or may be bent inother directions, and, in yet other embodiments, the barbed holder 600may have barbs protruding from the encapsulated source 610 in multipledirections. In an embodiment, a staple clip may be fabricated by weldinga 0.25 mm diameter wire axially parallel to the leg of the clip. Thepointed end may be cut with wire clippers and then ground using a finegrinding stone attachment to a grinding device.

FIG. 7 is a schematic illustration of a barbed holder 700 havingmultiple barbs 701, 702, 703 in an array on one side of the barbedholder 700 according to another embodiment of the system describedherein. In various embodiments, the multiple barbs 701, 702, 703 may beon one or both ends. The illustrated embodiment shows an array of barbs701, 702, 703 protruding from one side of the holder 700. Additionally,the illustrated embodiment shows additionally and/or alternativelymultiple barbs 711, 712 protruding from an encapsulated radioactivesource 710 of the holder 700.

FIG. 8 is a schematic illustration of a barbed holder 800 havingmultiple barbs 801, 802, 803 protruding in multiple directions from thebarbed holder according to an embodiment of the system described herein.In various embodiments, the multiple barbs 801, 802, 803 may be on oneor both ends, and the barbs 801, 802, 803 may be disposed in differentlocations and orientations. The illustrated embodiment shows an array ofbarbs 701, 702, 703 protruding from multiple sections of the holder 800.Additionally, the illustrated embodiment shows additionally and/oralternatively multiple barbs 811, 812 protruding in different directionsfrom an encapsulated radioactive source 810 of the holder 800.

FIG. 9 is a schematic illustration of a barbed holder 800 comprised ofmultiple barbs 901, 902, 903 disposed on a helical coil like thatdescribed elsewhere herein to prevent the coil, with encapsulatedradioactive source 910, from unscrewing and/or otherwise dislodging fromthe tissue according to an embodiment of the system described herein.

In various embodiment, the helical coil embodiment as illustrated may befabricated from a single length of wire by bending and coiling the wireinto the desired configuration with the radioactive encapsulationattached at one end. Alternatively, the helical coil embodiment maybefabricated from one length of wire by bending and coiling the wire intothe desired configuration with the radioactive encapsulation attached atone end, and with another length of wire, bent and coiled to the desiredconfiguration, attached to the other end. In other embodiments, thehelical coil and/or barbed holder embodiments may be fabricated bycasting metal into a desired shape, by molding a polymer material intothe desired shape, by 3D printing from metal, plastic, or a combination,and/or by being over-molded onto an existing device, among otherpossible fabrication techniques.

The barbed protrusions may also be fabricated in a variety of ways. Inone embodiment, the barb can be fabricated by machining from a solidpiece of material. Alternatively, the barbed protrusion may befabricated by casting metal into the desired shape. Alternatively, thebarbed protrusion may be fabricated by molding a polymer into thedesired shape, by roll-forming, and/or by stamping, among other possiblefabrication techniques.

FIGS. 10A-10C shows formation of a barbed protrusion on a barbed holder1000 according to an embodiment of the system described herein. A barbedprotrusion 1001 a may be initially formed by bending a protruding wireback upon itself (FIG. 10A). The two now-parallel wires of theprotrusion 1001 b may be welded together over a short distance (FIG.10B). The end can then be ground or possibly shaped by laser cutting, orby machining to form the finalized barbed protrusion 1001 c (FIG. 10C).

FIG. 11 is a schematic illustration showing that a barbed protrusion1101 may be formed on one end of a barbed holder 1100 and the other endof the holder 1100, with a radioactive source 1110 therebetween, beingsimply plugged according to an embodiment of the system describedherein.

FIG. 12 is a schematic illustration showing a barbed holder 1200 withmultiple end protrusions 1201, 1202 according to an embodiment of thesystem described herein. The protrusion 1201 may be barbed for insertionof the holder 1200 and radioactive source 1210 into tissue as discussedelsewhere herein. In order to preclude the radioactive source migratingin the forward direction because of lack of any retarding resistance,the protrusion 1202 may be formed from a second bent wire incorporatedonto the opposite end. In this embodiment, the protrusion 1201 may berequired to be sharp, as it would not be used for piercing the tissue,but only for retarding further forward movement.

FIG. 13 is a schematic illustration showing a barbed holder 1300 showingmultiple protrusions 1301, 1302 in which both of the protrusions 1301,1302 are formed to be pointed, which would permit the holder 1300 andradioactive source 1310 to be inserted in either direction according toan embodiment of the system described herein. This embodiment mayadvantageously eliminate the need for orientation in the deliveryneedle.

FIGS. 14A-14C are schematic illustrations showing embodiments forfabrication of a barb for a barbed holder according to the systemdescribed herein. FIG. 14A shows that a barb 1401 may be fabricated bymachining to its final configuration. Alternatively, as shown in FIG.14B, a barb 1402 could be fabricated by machining, or cutting, orstamping in a flat configuration. As shown in FIG. 14C, a barb 1403 maythen be manufactured by further bending the barb 1402 into a finaldesired shape.

FIGS. 15A and 15B shows a barbed holder 1500 in which a barb is attachedto the holder 1500 by welding to a protrusion from the body of thesource encapsulation according to an embodiment of the system describedherein. FIG. 15B shows a side view of the barbed holder or harpoon ofFIG. 15A. The barbed holder 1500 is appended to an encapsulatedradioactive source 1510.

FIG. 16 is a flow diagram 1600 for a method for producing an implantabledevice for brachytherapy according to one or more embodiments of thesystem described herein. At a step 1602, an insertable member of theimplantable device is formed from material that is suitable forinsertion into desired tissue for brachytherapy. In various embodiments,the insertable member may be substantially cylindrical and may be madeof a single wire and/or may be a harpoon shape. After the step 1602, ata step 1604, a fixation element is incorporated into and/or affixed tothe insertable member. In various embodiments, the fixation element maybe a helical coil shape configuration of the insertable member and/ormay be at least one barbed protrusion affixed to at least section of theinsertable member. In other embodiments, the fixation element may resultfrom a memory alloy material of which the insertable member ismanufactured, such that the fixation element of the insertable member isthe shape into which the insertable member forms after implantation ofthe implantation device. After the step 1604, at a step 1606, aradioactive source is encapsulated into the implantable device. Invarious embodiments, the radioactive source may be completely orpartially encapsulated within the insertable member, such as within achamber thereof and/or otherwise incorporated into and/or appended tothe insertable member. In other embodiments, the radioactive source maybe completely or partially encapsulated within the fixation element. Itis noted that any of the above-noted steps may be performed in adifferent order. After the step 1606, processing is complete.

FIG. 17 is a flow diagram 1700 for a method for brachytherapy accordingto an embodiment of the system described herein. At a step 1702, acavity within a body of tissue is identified. For example, a portion oftumorous tissue within a body of tissue may be removed so as to generatethe cavity. After the step 1702, at a step 1704, an implantable deviceis inserted into or adjacent to the cavity. The implantable device maybe formed and/or configured as one or more of the embodiments discussedherein and, specifically, may having a fixation element and at least oneradioactive source encapsulated within the implantable device, asdiscussed in detail elsewhere herein. After the step 1704, at a step1706, the implantable device is fixedly disposed such that theradioactive source is positioned for delivering radiation therapy to thedesired tissue. The fixation element and the radioactive source may beimplemented as one or more of the embodiments discussed herein. Forexample, the fixation may occur as a result of post-implantation thermalprocessing where the implantable device is made of a memory alloy. Afterthe step 1706, processing is complete.

In another embodiment of the system described herein, one or morecomponents of the implantable device, e.g., the insertable memberholding the radioactive source and/or one or more elements of theinsertable member, may be a bio-resorbable component made of abio-resorbable material. In this example, the one or more bio-resorbablecomponents of the implantable device may dissolve and/or be absorbed inthe body after the therapeutic dose has been delivered. This embodimentusing the one or more bio-resorbable components may be appropriatelyused in connection with any one of more of the embodiments of the systemdescribed herein.

In yet another embodiment of the system described herein, one or morecomponents of the implantable device, e.g., the insertable memberholding the radioactive source and/or any one or more elements of theinsertable member, may include a drug eluting component, such as a drugeluting member and/or a drug eluting device. In this example, the drugeluting component of the implantable device may provide drugs to enhancethe radiation dose effects to cancer cells and/or provide drugs toprotect healthy cells from the radiation doses of the implantabledevice. This embodiment using the drug eluting component may beappropriately used in connection with any one of more of the embodimentsof the system described herein.

Various embodiments discussed herein may be combined with each other inappropriate combinations in connection with the system described herein.Additionally, in some instances, the order of steps in the flowdiagrams, flowcharts and/or described flow processing may be modified,where appropriate. Further, it is noted that various aspects of thesystem described herein may be implemented using software, hardware, acombination of software and hardware and/or other computer-implementedmodules or devices having the described features and performing thedescribed functions. For example, aspects of manufacture of the systemdescribed herein and/or of implanting of the implantable device atdesired locations according to the embodiments of the system describedherein may be implemented in connection with the use of software and/orother computer components to provide levels of design or control ofaspects of the system described herein. In this regard, softwareimplementations of aspects of the system described herein may includeexecutable code that is stored in a computer-readable medium andexecuted by one or more processors. The computer-readable medium mayinclude volatile memory and/or non-volatile memory, and may include, forexample, a computer hard drive, ROM, RAM, flash memory, portablecomputer storage media such as a CD-ROM, a DVD-ROM, an SD card, a flashdrive or other drive with, for example, a universal serial bus (USB)interface, and/or any other appropriate tangible or non-transitorycomputer-readable medium or computer memory on which executable code maybe stored and executed by a processor. The system described herein maybe used in connection with any appropriate operating system.

Other embodiments of the invention will be apparent to those skilled inthe art from a consideration of the specification or practice of theinvention disclosed herein. It is intended that the specification andexamples be considered as exemplary only, with the true scope and spiritof the invention being indicated by the following claims.

What is claimed is:
 1. An implantable device for brachytherapy,comprising: an insertable member having a first end and a second end, acentral section positioned between the ends, and a fixation element thatretains the implantable device in an inserted position within tissue;and a radioactive source disposed within the insertable member, whereinthe insertable member is made of a memory alloy, and wherein thefixation element includes a straight configuration of the insertablemember prior to insertion into the inserted position within the tissueand a non-straight configuration into which the insertable member formsafter insertion into the inserted position, wherein the fixation elementforms into a helical coil configuration after insertion of theinsertable member.
 2. The implantable device according to claim 1,wherein the memory alloy is Nickel Titanium or nitinol.
 3. Theimplantable device according to claim 1, wherein the fixation elementincludes at least one barbed protrusion on at least one of the ends ofthe insertable member.
 4. The implantable device according to claim 1,wherein the fixation element includes a plurality of barbed protrusionson the insertable member.
 5. The implantable device according to claim1, wherein the radioactive source is encapsulated within the insertablemember.
 6. The implantable device according to claim 5, wherein theradioactive source is completely encapsulated within the insertablemember.
 7. The implantable device according to claim 5, wherein theinsertable member includes a chamber with at least one cut-out forexternal accessibility, and wherein the radioactive source is partiallyencapsulated within the insertable member by being disposed within thechamber with the at least one cut-out.
 8. The implantable deviceaccording to claim 1, wherein the radioactive source is encapsulatedwithin the fixation element.
 9. The implantable device according toclaim 1, wherein the radioactive source includes a radioactive nuclideselected from at least one of: palladium-103, iodine-125,gadolinium-153, samarium-145, cesium-131 or ytterbium-169.
 10. Theimplantable device according to claim 1, wherein the insertable memberincludes at least one of: a bio-resorbable component or a drug elutingcomponent.
 11. An implantable device for brachytherapy, comprising: aninsertable member having a first end and a second end, a central sectionpositioned between the ends, and a fixation element that retains theimplantable device in an inserted position within tissue; and aradioactive source disposed within the insertable member, wherein theinsertable member is made of a memory alloy, and wherein the fixationelement includes a straight configuration of the insertable member priorto insertion into the inserted position within the tissue and anon-straight configuration into which the insertable member forms afterinsertion into the inserted position, wherein the fixation elementincludes at least one barbed protrusion, and wherein the radioactiveelement is encapsulated within at least a portion of the at least onebarbed protrusion.
 12. The implantable device according to claim 11,wherein the memory alloy is Nickel Titanium or nitinol.
 13. Theimplantable device according to claim 11, wherein the fixation elementincludes a plurality of barbed protrusions on the insertable member. 14.The implantable device according to claim 11, wherein the radioactivesource is completely encapsulated within the insertable member.
 15. Theimplantable device according to claim 11, wherein the insertable memberincludes a chamber with at least one cut-out for external accessibility,and wherein the radioactive source is partially encapsulated within theinsertable member by being disposed within the chamber with the at leastone cut-out.
 16. The implantable device according to claim 11, whereinthe radioactive source is encapsulated within the fixation element. 17.The implantable device according to claim 11, wherein the radioactivesource includes a radioactive nuclide selected from at least one of:palladium-103, iodine-125, gadolinium-153, samarium-145, cesium-131 orytterbium-169.
 18. The implantable device according to claim 11, whereinthe insertable member includes at least one of: a bio-resorbablecomponent or a drug eluting component.
 19. A method of manufacturing animplantable device for brachytherapy, comprising: forming an insertablemember of the implantable device for insertion into an area of tissue;encapsulating a radioactive source in the implantable device; andincorporating a fixation element into the insertable member for fixingthe radioactive source at a desired location in the area of the tissue,wherein the insertable member is made of a memory alloy and wherein thefixation element includes a straight configuration of the insertablemember prior to insertion into the inserted position within the tissueand a non-straight configuration into which the insertable member formsafter insertion into the inserted position, wherein the fixation elementforms into a helical coil configuration after insertion of theinsertable member.
 20. The method according to claim 19, wherein thefixation element is at least one barbed protrusion on the insertablemember.
 21. The method according to claim 19, wherein the radioactivesource is completely encapsulated in the insertable member or thefixation element.
 22. A method for performing brachytherapy, comprising:identifying an area of tissue for brachytherapy; inserting animplantable device into the area of the tissue, wherein the implantabledevice includes a fixation element and a radioactive source encapsulatedwithin the implantable device; and fixedly disposing the implantabledevice using the fixation element such that the radioactive source isfixed in a position for delivering radiation therapy to the area oftissue, wherein the implantable device is made of a memory alloy, andwherein the implantable device is fixedly disposed by thermal processingafter inserting the implantable device into the area of the tissue andwherein the fixation element includes a straight configuration of theimplantable device prior to insertion into the inserted position withinthe tissue and a non-straight configuration into which the implantabledevice forms after insertion into the inserted position, wherein theimplantable device forms into a helical coil shape after insertion intothe inserted position.
 23. The method according to claim 22, wherein theimplantable device further includes at least one barbed protrusion on atleast one end of the implantable device.